Choroidal Imaging Offers a New Window on Disease Management

The choroid, the vascular layer of the eye, plays
important roles in ocular anatomy and function,
providing nutrition and support to the retina.
It also plays a role in the pathophysiology of
many posterior segment diseases. Our ability to visualize
the choroid has historically been limited because of its
location deep in the eye, behind the pigmented tissues
of the retina. Traditional imaging modes for visualizing
this anatomic layer have included ultrasound, with its
limited resolution, and vascular-based modalities such
as indocyanine green (ICG) angiography. Although optical
coherence tomography (OCT) revolutionized the
imaging of the retina during the preceding decade,1 the
choroid remained for the most part out of range for this
technology as conventionally applied.

Beginning in 2008, Richard F. Spaide, MD, and colleagues2,3
opened a new window on the choroid and its
pathologies with their description of enhanced depth
imaging (EDI) OCT. By positioning a spectral domain
(SD) OCT device (Spectralis, Heidelberg Engineering)
closer to the eye than is done in normal practice, they
obtained an inverted image with the most tightly
focused illumination at the level of the choroid or inner
sclera.2 In their investigations, Spaide and colleagues
obtained inverted images of sections composed of 100
averaged scans from a rectangle focused over the fovea
or other area of interest. This group has used EDI-OCT
to measure the mean choroidal thickness in healthy
volunteers2<> and in myopic eyes,4 and to evaluate the
association of choroidal thickness with age.3 The investigators
have also used this technology to assess the
condition of the choroid in numerous pathologies,
including retinal pigment epithelial detachment in agerelated
macular degeneration (AMD),5 central serous
chorioretinopathy (CSC),6,7 dome-shaped macula,8 and
a newly described clinical entity, age-related choroidal
atrophy (Figures 1-5).9

MORE ACCESSIBLE

Many other centers have since published their
own observations using EDI, and the bibliography for
this new technology is lengthening almost daily as
clinicians explore its implications. Manufacturers of SD-OCT equipment quickly realized the implications
of EDI for their customers and have introduced features
to allow clinicians to take advantage of its capabilities
more easily.

One of the first things manufacturers did to improve
the use of EDI was to allow users to flip the images. A
result of moving the OCT unit closer to the eye, and
thus the choroid closer to the zero-delay line, is that the
resulting image is flipped—it appears upside-down compared
to the way we have become accustomed to seeing
OCT images. When EDI-OCT was first described, we
simply looked at the images upside down. But the companies
soon introduced software to re-flip the images so
that we can view them as we normally would.

Another change has been the introduction of signal
averaging by more manufacturers. The Heidelberg
Spectralis has always included signal-averaging capabilities,
but other companies have added signal averaging
capabilities to their software. This is a relatively easy
feature to add because signal averaging is simply a mathematic
subtraction, a photographic principle.

The combination of image flipping and signal averaging
(these features are given various names by different
manufacturers) now provides devices that were not
originally designed for EDI the ability to perform it. The
newer software makes it easier for the average photographer
to do EDI, and as a result this imaging modality is
rapidly becoming more accessible.

The Ophthalmic Imaging Center at the Cole Eye
Institute is investigating the use of EDI-OCT for a number
of applications, and clinicians here and elsewhere
are using the technology to manage diseases in ways we
never could before.

SEEING CSC

Perhaps the greatest utility to date for EDI-OCT from
a clinical standpoint is in the diagnosis and management
of CSC. In this past, we would have used ICG
imaging to diagnose and follow CSC, but now we are
able to use EDI.

EDI has proven to be helpful in a number of patients
we have seen lately for second opinions regarding anti-
VEGF therapy. Say, for example, a 60-year-old woman
presents for a second opinion with subretinal fluid, a
pigment epithelial detachment, and drusen visible on
standard SD-OCT. She is being treated with anti-VEGF
therapy but has not experienced improvement in her
visual acuity. On EDI-OCT we see a grossly thickened
choroid, consistent with CSC. In AMD, EDI investigations
have shown, the choroid is not thickened, but rather
significantly thinner compared with age- and refractionmatched
controls.10

In this case, therefore, anti-VEGF therapy is not beneficial.
For this patient, if her vision is good, we would
observe, or if the vision is poor we might perform photodynamic
therapy, a more appropriate treatment for CSC.
In this case EDI helped us change a misdiagnosis to the
correct diagnosis.

OTHER CONDITIONS, AND QUESTIONS

We have found EDI helpful in following a number of
pathologic conditions. For instance the uveitides; EDI
is useful in patients with uveitic pathologies, such as
Vogt-Koyanagi-Harada syndrome, to assess whether the
inflammation is responding to steroid or immunomodulatory
therapy.

In a number of pathologies the choroid is thinned, but
the reasons for and implications of the thinning are so
far poorly understood. Thinning of the choroid is seen in
eyes with AMD, glaucoma, and diabetic retinopathy,10 as
well as in retinitis pigmentosa and other hereditary retinal
degenerations.11 It has also been observed that the
choroid thins with anti-VEGF therapy for AMD.12

The implications of these findings are not clear. Is
the anti-VEGF therapy related to decreased choroidal
blood flow; is that what is thinning the choroid? Is the
thinning we see in the hereditary conditions a function
of the retinal degeneration, or is it the other way
around; is the choroidal thinning somehow causative
of the retinal degeneration? These questions remain to
be answered.

Currently, this technology is being used mostly to
assess single-point subfoveal choroidal thickness, but
hopefully in the future it will help us to differentiate,
for example, the roles of choriocapillaris vs larger choroidal
vessels in a particular pathophysiology. Other
questions, too, such as whether thickness variations
among patients have prognostic significance, require
investigation.

LOOKING TO THE FUTURE

Because of Spaide and colleagues’ innovation in optimizing
the choroidal position relative to the zero delay
line, as well as the higher speed capabilities of newer OCT
devices that allow signal averaging, we now have a new
window on the choroid. As we improve our use of EDI,
our needs for other imaging modalities may diminish.

With increased vision, of course, has come the realization
that the more we can see, the more questions we
have. It is hoped that EDI will eventually help us to find
the answers.

In addition, new technologies such as higher speeds
and longer laser wavelengths will help us to further improve the visibility of the choroid. For example, Carl
Zeiss Meditec has an experimental OCT device using a
1050-nm light source that allows even deeper penetration
into the choroid. It peers so deep into the eye, in
fact, that in some cases we can see the retrobulbar space.
The images from this device are spectacular.

The next frontier currently being investigated at
the Cole Eye Institute is choroidal area and choroidal
volume. Just as we can use conventional SD-OCT to
generate area and volume for the retina, with the right
analysis software we can do the same for the choroid.
Most investigators to date have been looking at singlepoint
thickness of the choroid. Will it be advantageous
to look at choroidal volume in a 6-by-6 area? Will these
images correlate better with disease findings? These are
all areas that the Ophthalmic Imaging Center at the
Cole Eye Institute is working on.

The most exciting thing, however, is that we already
can see things we never could before. Clinicians are
using this technology routinely to diagnose and manage
patients with CSC, uveitis, choroidal tumors, and other
conditions. Considering that this imaging modality was
described less than 5 years ago, we must assume that we
are only on the tip of the iceberg regarding the potential
for this technology. We look forward to probing deeper
into the choroid with the aid of EDI-OCT.

Peter K. Kaiser, MD, is a Professor of
Ophthalmology at the Cleveland Clinic Lerner
College of Medicine and a staff surgeon in
the Vitreoretinal Department at the Cole Eye
Institute, Cleveland Clinic. He is a Retina Today
Editorial Board member. Dr. Kaiser states that he is a
speaker for Carl Zeiss Meditec and Optovue and a consultant
to Heidelberg Engineering. Dr. Kaiser may be reached
at pkkaiser@aol.com.

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Retina Today is a publication that delivers the latest research and clinical developments from areas such as medical retina, retinal surgery, vitreous, diabetes, retinal imaging, posterior segment oncology and ocular trauma. Each issue provides insight from well-respected specialists on cutting-edge therapies and surgical techniques that are currently in use and on the horizon.